Patients with acute kidney injury (AKI) during immune checkpoint inhibitor therapy have increased risks for death, results of a recent meta-analysis show.

Investigators performed a meta-analysis of 7 studies including 895 patients with AKI and 2872 patients without AKI receiving immune checkpoint inhibitors. In analyses of 5 studies, AKI during immune checkpoint inhibitor therapy was significantly associated with a 42% increased risk of all-cause mortality, compared with no AKI, Mehmet Kanbay, MD, of Koc University School of Medicine in Istanbul, Turkey, and colleagues reported in Clinical Kidney Journal. The investigators observed a trend toward higher death risk with stage 3 AKI compared with lower stages.

In analyses of 2 studies, patients with persistent AKI without recovery had a significant 2.9-fold increased risk for death compared with patients with AKI recovery. Complete AKI recovery was defined as serum creatinine less than 0.35 mg/dL, but 1 study also included partial AKI recovery.

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“Even though these results are not definitive, they emphasize the need for clear management guidelines for AKI during the course of immune checkpoint inhibitor therapy,” Dr Kanbay’s team wrote. “Moreover, the early recognition and proper management may improve the clinical outcome.”

The investigators urged future large-scale randomized studies on AKI during immune checkpoint inhibitor therapy to better understand this issue and possible therapeutic alternatives.

In a second study published in Clinical Kidney Journal, Alexandre O. Gérard, MD, PhD student, of University Hospital Centre of Nice in France, and colleagues suggest immune checkpoint inhibitor therapy may be a “second hit” that precipitates AKI provoked by another nephrotoxic drug. They compared 167 cases of AKI and 668 cases of extrarenal immune-related adverse events only during immune checkpoint inhibitor therapy. The investigators found that AKI was more likely to develop in patients with concomitant use of fluindione (a vitamin K antagonist), nonsteroidal anti-inflammatory drugs, and proton pump inhibitors. Older age and chronic kidney disease were nonmodifiable risk factors for AKI during immune checkpoint inhibitor therapy.

In the review by Dr Kanbay and colleagues, the patients had a mean age of 61-67 years. The proportion of patients with AKI stages 1, 2, and 3 and the need for renal replacement therapy varied widely across studies. Hypertension was present in 34%-60% of the overall cohort and diabetes in 9%-19%. Nondialysis-dependent chronic kidney disease affected 10%-30%.

Lung cancer and melanoma were the most frequent neoplasms in both papers. The studies varied in the types of immune checkpoint inhibitor investigated.

Among the limitations of the meta-analysis, included studies did not probe other possible contributors to AKI, such as volume depletion, other potentially nephrotoxic medications, and infections.


Kanbay M, Copur S, Siriopol D, et al. The association between acute kidney injury and outcomes in cancer patients receiving immune checkpoint inhibitor therapy: a systematic review and meta-analysis. Clin Kidney J. Published online August 31, 2022. doi:10.1093/ckj/sfac194

Gérard AO, Barbosa S, Parassol N, et al. Risk factors associated with immune checkpoint inhibitor–induced acute kidney injury compared with other immune-related adverse events: a case–control study. Clin Kidney J. 15(10):1881-1887. doi:10.1093/ckj/sfac109